Studies on a three-step preparation of beta-fluoroalkyl acrylates from fluoroacetic esters

Beta-Fluoroalkyl-acrylic esters are valuable building blocks for the synthesis of organofluorine compounds. Although the preparation of several beta-fluoroalkyl-acrylates is known, a general and straightforward lab-scale methodology for the preparation of multigram amounts of these compounds from fluoroacetic esters is not available, and the related chemistry has not been investigated in detail. We now describe an optimized three-step protocol relying on: (1) Claisen-type condensation of fluoroacetic esters with ethyl acetate, using LDA as base; (2) reduction of the resulting gamma-fluoro-beta-keto esters by NaBH4, using toluene or benzene as solvents; (3) P2O5-promoted dehydration of the intermediate gamma-fluoro-beta-hydroxy esters. The methodology affords preparatively useful yields of the target compounds incorporating only fluorine atoms (CF3, CHF2, C2F5), whereas the gamma-halodifluoromethyl (CCIF2, CBrF2, CIF2) acrylates could not be obtained in analytically pure form from the dehydration step.